AUTHOR=Chan Sze Wa , Chu Tanya T. W. , Ho Chung Shun , Kong Alice P. S. , Tomlinson Brian , Zeng Weiwei 

TITLE=Influence of CYP2D6 and CYP3A5 Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Bisoprolol in Hypertensive Chinese Patients

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.683498

DOI=10.3389/fmed.2021.683498

ISSN=2296-858X

ABSTRACT=<p><bold>Purpose:</bold> This study was performed to investigate the effects of common polymorphisms in <italic>CYP2D6</italic> and <italic>CYP3A5</italic> on the plasma concentrations and antihypertensive effects of bisoprolol in hypertensive Chinese patients.</p><p><bold>Methods:</bold> One hundred patients with essential hypertension were treated with open-label bisoprolol 2.5 mg daily for 6 weeks. Clinic blood pressure (BP) and ambulatory BP (ABP) were measured after the placebo run-in and after 6 weeks treatment. Peak plasma concentrations of bisoprolol were measured at 3 h after the first dose and 3 h after the dose after 6 weeks treatment. Trough levels were measured before the dose after 6 weeks treatment. Bisoprolol plasma concentrations were measured with a validated liquid chromatography tandem mass spectrometry method. Six common polymorphisms in <italic>CYP2D6</italic> and the <italic>CYP3A5</italic><sup>*</sup><italic>3</italic> polymorphism were genotyped by TaqMan® assay.</p><p><bold>Results:</bold> After 6 weeks of treatment, clinic BP and heart rate were significantly reduced by 14.3 ± 10.9/8.4 ± 6.2 mmHg (<italic>P</italic> &lt; 0.01) and 6.3 ± 7.6 BPM (<italic>P</italic> &lt; 0.01), respectively. Similar reductions were seen in ABP values. Bisoprolol plasma concentration at 3 h after the first dose and 3 h post-dose after 6 weeks of treatment were significantly associated with baseline body weight (<italic>P</italic> &lt; 0.001) but there was no significant effect of the <italic>CYP2D6</italic> and <italic>CYP3A5</italic> polymorphisms on these or the trough plasma concentrations. There was no significant association of the <italic>CYP2D6</italic> and <italic>CYP3A5</italic> polymorphisms or plasma bisoprolol concentrations with the clinic BP or ABP responses to bisoprolol.</p><p><bold>Conclusion:</bold> Bisoprolol 2.5 mg daily effectively reduced BP and HR. The common polymorphisms in <italic>CYP2D6</italic> that were examined and the <italic>CYP3A5</italic><sup>*</sup><italic>3</italic> polymorphism appear to have no benefit in predicting the hemodynamic response to bisoprolol in these patients.</p>